996 resultados para pharmaceutical reference pricing
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No literature data above atmospheric pressure could be found for the viscosity of TOTIVI. As a consequence, the present viscosity results could only be compared upon extrapolation of the vibrating wire data to 0.1 MPa. Independent viscosity measurements were performed, at atmospheric pressure, using an Ubbelohde capillary in order to compare with the vibrating wire results, extrapolated by means of the above mentioned correlation. The two data sets agree within +/- 1%, which is commensurate with the mutual uncertainty of the experimental methods. Comparisons of the literature data obtained at atmospheric pressure with the present extrapolated vibrating-wire viscosity measurements have shown an agreement within +/- 2% for temperatures up to 339 K and within +/- 3.3% for temperatures up to 368 K. (C) 2014 Elsevier B.V. All rights reserved.
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In Part I of the present work we describe the viscosity measurements performed on tris(2-ethylhexyl) trimellitate or 1,2,4-benzenetricarboxylic acid, tris(2-ethylhexyl) ester (TOTM) up to 65 MPa and at six temperatures from (303 to 373)K, using a new vibrating-wire instrument. The main aim is to contribute to the proposal of that liquid as a potential reference fluid for high viscosity, high pressure and high temperature. The present Part II is dedicated to report the density measurements of TOTM necessary, not only to compute the viscosity data presented in Part I, but also as complementary data for the mentioned proposal. The present density measurements were obtained using a vibrating U-tube densimeter, model DMA HP, using model DMA5000 as a reading unit, both instruments from Anton Paar GmbH. The measurements were performed along five isotherms from (293 to 373)K and at eleven different pressures up to 68 MPa. As far as the authors are aware, the viscosity and density results are the first, above atmospheric pressure, to be published for TOTM. Due to TOTM's high viscosity, its density data were corrected for the viscosity effect on the U-tube density measurements. This effect was estimated using two Newtonian viscosity standard liquids, 20 AW and 200 GW. The density data were correlated with temperature and pressure using a modified Tait equation. The expanded uncertainty of the present density results is estimated as +/- 0.2% at a 95% confidence level. Those results were correlated with temperature and pressure by a modified Tait equation, with deviations within +/- 0.25%. Furthermore, the isothermal compressibility, K-T, and the isobaric thermal expansivity, alpha(p), were obtained by derivation of the modified Tait equation used for correlating the density data. The corresponding uncertainties, at a 95% confidence level, are estimated to be less than +/- 1.5% and +/- 1.2%, respectively. No isobaric thermal expansivity and isothermal compressibility for TOTM were found in the literature. (C) 2014 Elsevier B.V. All rights reserved.
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The paper proposes a Flexibility Requirements Model and a Factory Templates Framework to support the dynamic Virtual Organization decision-makers in order to reach effective response to the emergent business opportunities ensuring profitability. Through the construction and analysis of the flexibility requirements model, the network managers can achieve and conceive better strategies to model and breed new dynamic VOs. This paper also presents the leagility concept as a new paradigm fit to equip the network management with a hybrid approach that better tackle the performance challenges imposed by the new and competitive business environments.
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The Janssen-Cilag proposal for a risk-sharing agreement regarding bortezomib received a welcome signal from NICE. The Office of Fair Trading report included risk-sharing agreements as an available tool for the National Health Service. Nonetheless, recent discussions have somewhat neglected the economic fundamentals underlying risk-sharing agreements. We argue here that risk-sharing agreements, although attractive due to the principle of paying by results, also entail risks. Too many patients may be put under treatment even with a low success probability. Prices are likely to be adjusted upward, in anticipation of future risk-sharing agreements between the pharmaceutical company and the third-party payer. An available instrument is a verification cost per patient treated, which allows obtaining the first-best allocation of patients to the new treatment, under the risk sharing agreement. Overall, the welfare effects of risk-sharing agreements are ambiguous, and care must be taken with their use.
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Human exposure to Bisphenol A (BPA) results mainly from ingestion of food and beverages. Information regarding BPA effects on colon cancer, one of the major causes of death in developed countries, is still scarce. Likewise, little is known about BPA drug interactions although its potential role in doxorubicin (DOX) chemoresistance has been suggested. This study aims to assess potential interactions between BPA and DOX on HT29 colon cancer cells. HT29 cell response was evaluated after exposure to BPA, DOX, or co-exposure to both chemicals. Transcriptional analysis of several cancer-associated genes (c-fos, AURKA, p21, bcl-xl and CLU) shows that BPA exposure induces slight up-regulation exclusively of bcl-xl without affecting cell viability. On the other hand, a sub-therapeutic DOX concentration (40nM) results in highly altered c-fos, bcl-xl, and CLU transcript levels, and this is not affected by co-exposure with BPA. Conversely, DOX at a therapeutic concentration (4μM) results in distinct and very severe transcriptional alterations of c-fos, AURKA, p21 and CLU that are counteracted by co-exposure with BPA resulting in transcript levels similar to those of control. Co-exposure with BPA slightly decreases apoptosis in relation to DOX 4μM alone without affecting DOX-induced loss of cell viability. These results suggest that BPA exposure can influence chemotherapy outcomes and therefore emphasize the necessity of a better understanding of BPA interactions with chemotherapeutic agents in the context of risk assessment.
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Brain dopamine transporters imaging by Single Emission Tomography (SPECT) with 123I-FP-CIT (DaTScanTM) has become an important tool in the diagnosis and evaluation of Parkinson syndromes.This diagnostic method allows the visualization of a portion of the striatum – where healthy pattern resemble two symmetric commas - allowing the evaluation of dopamine presynaptic system, in which dopamine transporters are responsible for dopamine release into the synaptic cleft, and their reabsorption into the nigrostriatal nerve terminals, in order to be stored or degraded. In daily practice for assessment of DaTScan TM, it is common to rely only on visual assessment for diagnosis. However, this process is complex and subjective as it depends on the observer’s experience and it is associated with high variability intra and inter observer. Studies have shown that semiquantification can improve the diagnosis of Parkinson syndromes. For semiquantification, analysis methods of image segmentation using regions of interest (ROI) are necessary. ROIs are drawn, in specific - striatum - and in nonspecific – background – uptake areas. Subsequently, specific binding ratios are calculated. Low adherence of semiquantification for diagnosis of Parkinson syndromes is related, not only with the associated time spent, but also with the need of an adapted database of reference values for the population concerned, as well as, the examination of each service protocol. Studies have concluded, that this process increases the reproducibility of semiquantification. The aim of this investigation was to create and validate a database of healthy controls for Dopamine transporters with DaTScanTM named DBRV. The created database has been adapted to the Nuclear Medicine Department’s protocol, and the population of Infanta Cristina’s Hospital located in Badajoz, Spain.
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The DatScanTM and its Semiquantification (SQ) can provide advantages in the diagnosis of Parkinsonian Syndromes (PS). To improve the SQ is recommended the creation of adapted database (DB) with reference values for the Nuclear Medicine Departments. Previously to this work was created a adapted database (DBRV) to Nuclear Medicine Department's protocol and population of Infanta Cristina's Hospital located in Badajoz, for patients between the ages of 60 and 75, and reference values of the SQ were calculated. Aim: To evaluate the discrimination capacity of a department's adapted DB reference's values of healthy controls for DatScanTM.
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Semi quantification (SQ) in DaTScan® studies is broadly used in clinic daily basis, however there is a suspicious about its discriminative capability, and concordance with the diagnostic classification performed by the physician. Aim: Evaluate the discriminate capability of an adapted database and reference's values of healthy controls for the Dopamine Transporters (DAT) with 123I–FP-IT named DBRV adapted to Nuclear Medicine Department's protocol and population of Infanta Cristina's Hospital, and its concordance with the physician classification.
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The Pliensbachian/Toarcian boundary (Lower Jurassic) is well represented in the Lusitanian Basin (Portugal), mainly in the Peniche area, recorded by a marl/limestone series. Calcareous nannofossil assemblages are described herein, with the aim to contribute to the Toarcian GSSP definition. Marly samples were collected 3 m below and 7 m above this boundary and analysed for calcareous nannofossils. The main nannofossils observed were Biscutum finchii, B. grande, Calcivascularis jansae, Crepidolithus crassus, C. granulatus, C. impontus, Lotharingius hauffii, L. sigillatus, L. aff. L. velatus, Schizosphaerella spp. and Tubirhabdus patulus. This assemblage indicates that the Pliensbachian/Toarcian boundary in Peniche lies in the upper part of the NJ5b Subzone. Schizosphaerella and Lotharingius dominate the assemblage. The abundant occurrence of C. jansae and the common occurrence of B. grande indicate a strong Tethyan influence.
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M. tuberculosis-positive cultures were obtained from 228 patients seen in our service and drug sensitivity assays were carried out from January 1992 to December 1994. A survey of the medical records of these patients showed resistance to one or more drugs in 47 (20.6%), 25 of whom (10.9%), who reported previous treatment, were considered to have acquired resistance. Among the antecedents investigated, only previous treatment and alcoholism were the factors independently associated with the occurrence of resistance. The survival of patients with resistant strains was lower than that of patients attacked by non-resistant M. tuberculosis. We conclude that in the present series M. tuberculosis resistance to tuberculostatic agents was predominantly of the acquired type.
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The use of demand response programs enables the adequate use of resources of small and medium players, bringing high benefits to the smart grid, and increasing its efficiency. One of the difficulties to proceed with this paradigm is the lack of intelligence in the management of small and medium size players. In order to make demand response programs a feasible solution, it is essential that small and medium players have an efficient energy management and a fair optimization mechanism to decrease the consumption without heavy loss of comfort, making it acceptable for the users. This paper addresses the application of real-time pricing in a house that uses an intelligent optimization module involving artificial neural networks.
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The use of renewables have been increased I several countries around the world, namely in Europe. The wind power is generally the larger renewable resource with very specific characteristics in what concerns its variability and the inherent impacts in the power systems and electricity markets operation. This paper focuses on the Portuguese context of renewables use, including wind power. The work here presented includes the use of a real time pricing methodology developed by the authors aiming the reduction of electricity consumption in the moments of unexpected low wind power. A more specific example of application of real time pricing is demonstrated for the minimization of the operation costs in a distribution network. When facing lower wind power generation than expected from day ahead forecast, demand response is used in order to minimize the impacts of such wind availability change. In this way, consumers actively participate in regulation up and spinning reserve ancillary services through demand response programs.
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Dissertação apresentada para a obtenção do Grau de Doutor em Informática
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Recent changes of paradigm in power systems opened the opportunity to the active participation of new players. The small and medium players gain new opportunities while participating in demand response programs. This paper explores the optimal resources scheduling in two distinct levels. First, the network operator facing large wind power variations makes use of real time pricing to induce consumers to meet wind power variations. Then, at the consumer level, each load is managed according to the consumer preferences. The two-level resources schedule has been implemented in a real-time simulation platform, which uses hardware for consumer’ loads control. The illustrative example includes a situation of large lack of wind power and focuses on a consumer with 18 loads.
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Dissertation presented at Faculdade de Ciências e Tecnologia of Universidade Nova de Lisboa to obtain the Master degree in Electrical Engineering and Computer Science